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Future treatments for hepatitis delta virus infection
- Source :
- Liver International. 40:54-60
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Around 15-20 million people develop chronic hepatitis delta virus worldwide. Hepatitis delta virus (HDV) is a defective RNA virus requiring the presence of the hepatitis B virus surface antigen (HBsAg) to complete its life cycle. HDV infects hepatocytes using the hepatitis B virus (HBV) receptor, the sodium taurocholate cotransporting polypeptide (NTCP). The HDV genome is a circular single-stranded RNA which encodes for a single hepatitis delta antigen (HDAg) that exists in two forms (S-HDAg and L-HDAg), and its replication is mediated by the host RNA polymerases. The HBsAg-coated HDV virions contain a ribonucleoprotein (RNP) formed by the RNA genome packaged with small and large HDAg. Farnesylation of the L-HDAg is the limiting step for anchoring this RNP to HBsAg, and thus for assembling, secreting and propagating virion particles. There is an important risk of morbidity and mortality caused by end-stage liver disease and hepatocellular carcinoma with HDV and current treatment is pegylated-interferon (PEG-IFN) for 48 weeks with no other options in patients who fail treatment. The ideal goal for HDV treatment is the clearance of HBsAg, but a reasonably achievable goal is a sustained HDV virological response (negative HDV RNA 6 months after stopping treatment). New drug development must take into account the interaction of HBV and HDV. In this review, we will present the new insights in the HDV life cycle that have led to the development of novel classes of drugs and discuss antiviral approaches in phase II and III of development: bulevirtide (entry inhibitor), lonafarnib, (prenylation inhibitor) and REP 2139 (HBsAg release inhibitor).
- Subjects :
- Hepatitis B virus
HBsAg
viruses
Biology
Virus Replication
medicine.disease_cause
Antiviral Agents
Virus
03 medical and health sciences
Liver disease
0302 clinical medicine
medicine
Humans
Ribonucleoprotein
Hepatitis delta Antigens
Hepatitis B Surface Antigens
Hepatology
virus diseases
RNA
biochemical phenomena, metabolism, and nutrition
Hepatitis B
medicine.disease
Virology
Entry inhibitor
030220 oncology & carcinogenesis
Hepatocellular carcinoma
RNA, Viral
030211 gastroenterology & hepatology
Hepatitis Delta Virus
medicine.drug
Subjects
Details
- ISSN :
- 14783231 and 14783223
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Liver International
- Accession number :
- edsair.doi.dedup.....d723a28c844a281837e8ff0bf6963b7c